This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. This proposal encompasses the initial structure determination of medically relevant target proteins from the eukaryotic pathogens Trypanosoma bruci (African sleeping sickness). T. cruzi (Chagas disease), Leishmania spp. (leishmaniasis) and Plasmodium spp. (maleria), and follow-up screening of small molecule cocktails to identify chemical fragments that bind at the active site. Initial structure determinations will rely primarily on SeMet MAD/SAD phasing. Screening of cocktail soaks can be done at fixed wavelength, but benifits greatly from the use of robotic automounting and screening.